Nutrition plays a major role in atherogenesis, mediated in large part via alterations in lipoprotein metabolism. High density lipoprotein cholesterol (HDL-Chol) is a major predictor of coronary artery disease, yet little is known about dietary influences on HDL. We have shown before that weight loss and normalization of plasma triglycerides (TG) in hypertriglyceridemic men failed to elevate their initially low HDL-Chol. However, it is now known that HDL-Chol may not accurately reflect changes in HDL levels and composition under all conditions. Our purpose now is to study the influence of common dietary perturbations on HDL levels and composition in men with the genetically determined endogenous hypertriglyceridemia (and weight matched normal controls). We propose to test the following hypotheses: 1) In men with the genetic forms of hypertriglyceridemia, the normalization of TG levels by weight loss will fail to normalize low HDL-Chol levels. 2) Although HDL-Chol levels will not rise, significant changes in HDL composition and structure will nevertheless take place. 3) The failure of HDL-Chol to rise will be associated with decreased rates of VLDL-TG production and turnover in response to weight loss. We will study men on "normal American", high carbohydrate and high fat diets, before and after significant weight loss. Paired studies of VLDL-TG turnover, post-heparin and adipose tissue lipoprotein lipase, and detailed studies of HDL composition will be done. For compositional studies HDL subclasses will be isolated by zonal ultracentrifugation and lipids and apoproteins will be quantitated in detail using enzymatic and radioimmunoassay techniques respectively. From these studies we shall be able to relate VLDL metabolism to HDL levels and composition. The practical importance of this information is obvious, if alterations of HDL in plasma are important in the prevention or delay of clinical atherosclerosis.